JP2017193593A - Keratin treatment formulation and method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a formulation, kit, and method for rebuilding disulfide bonds in keratin found in hair, skin, or nails.SOLUTION: According to the present invention, there is provided a formulation comprising one or more active agents, which can treat hair that is damaged due to a hair coloring treatment and/or other reducing treatment, such as during a permanent wave. The formulations may be applied subsequent to a hair coloring treatment or simultaneously with a hair coloring treatment. Use of the active agent formulations during a permanent wave treatment prevents the reversion of the hair to its previous state, for at least one week, preferably at least three months, more preferably at least one year, most preferably greater than one year, after one or more applications of the formulation. Application of the active agent formulation to skin or nails can help repair damaged disulfide bonds due to natural wear and tear or natural aging.SELECTED DRAWING: None

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to US Provisional Application No. 61 / 994,709, filed May 16, 2014, the disclosure of which is incorporated herein by reference in its entirety. Is done.

  The present invention relates generally to formulations and methods for treating keratin in hair, skin or nails, in particular for strengthening and / or repairing hair during or after coloration or wave permanent treatment.

  Hair coloring is a fashion phenomenon that is now recognized worldwide. Examples of the coloring treatment include hair coloring, highlight treatment and bleaching treatment. Colored products can be classified into several types, including persistent, semi-persistent, somewhat persistent and temporary coloring formulations. Sustained hair coloring products dominate the global market.

  A great deal of effort has been devoted to developing various approaches to hair dyeing; these include oxidative dyes, direct acting dyes, natural dyes, metal dyes and reactive dyes. Many hair coloring formulations, particularly persistent coloring formulations, use reducing agents that break disulfide bonds in the hair and deepen hair coloring dyes and bleach treatment penetration into the hair.

  Disulfide bond chains in the hair can also be cleaved by the application of a reducing agent, such as during wave perm and the hair straightening process. After the disulfide bond is broken, the hair is placed under stress until the final style (eg, straight, wave or curl) is established and the disulfide bond is reestablished.

  Thioglycolic acid is often used, particularly as an ammonium salt, to break cysteine disulfide bonds present in hair. Sodium bisulfite is another example of a known reducing agent commonly used in various dyes and bleaching agents in color processing.

  Usually, oxidation is restored in part to restore the reduced bonds when an oxidizing agent such as hydrogen peroxide is present in the colored formulation and / or by exposing the hair to ambient oxygen. However, this oxidation process is very slow and may leave the hair curled or damaged.

  Similarly, hair undergoing wave permanent treatment is usually treated with a reducing agent followed by an oxidizing agent. Hydrogen peroxide is optionally added in the second step of restoring the hair to its previous state. The newly formed disulfide bonds in the treated hair are under stress to maintain the new shape of the hair; therefore, they are easily cleaved and the hairstyle reverts over time.

The use of peroxides in the hair styling process can damage the hair, remove non-natural colors from the hair, and / or curl the hair. In addition, some potential reduced thiols may remain in the hair even after the oxidation treatment. The hair styling treatment with peroxide involves reaction with the following thiol groups:
2K-SH + H ₂ O ₂ → KSKS + 2H ₂ O (Reaction I)
In the formula, K represents keratin in hair.

In the absence of two KSH groups to cause reaction I, the following reaction occurs, which is believed to damage hair:
K—S—H + H ₂ O ₂ → K—SO ₂ —OH (Reaction II).

  In addition to being a major component in hair, keratin is also a major component of the skin and nails. There are a number of different types of keratin, which are generally classified as soft or hard keratin. Soft keratin is abundant in skin, while hard keratin is abundant in hair and nails. The nails are particularly formed from modified keratins similar to those found in hair. The disulfide bond of keratin in the nail contributes to its impermeability. Therefore, if the keratin disulfide bridges present in the skin and nails are damaged, the skin or nails may become unhealthy and / or scaly. Therefore, maintaining keratin disulfide bridges helps keep the skin healthy and prevent cracking and cracking of the nails.

  When applying the color treatment, substantial improvements are required in the areas of saturation, color development, accurate initial color matching, improved wash fastness and improved hair conditioning. For example, maintaining the correct initial color with the hair for the desired period is still an elusive goal. Coloring formulations also cause severe hair damage, especially when the coloring process is repeated. In addition, various standard daily activities on the hair, such as hair brushing, hair blow drying, and sun exposure, can cause further damage to the hair.

  Wave permanent treatment can cause similar damage to hair. Improvements are also needed for hair damage repair and / or strengthening during or after such styling, both in the coloring and wave permanent processes. There is also a need for improved treatments and methods that can be applied to the skin and nails to repair damaged keratin.

  There is a need for hair formulations and treatments that repair and / or enhance keratin in hair that has been damaged from coloring and / or wave permanent treatments utilizing a reduction treatment.

  There is also a need for hair formulations and treatments that can repair potential reduced thiols present in the hair.

  There is also a need for formulations and treatments that can repair damage to keratin present in skin and hair.

  Accordingly, it is an object of the present invention to provide improved formulations and methods for repairing and / or strengthening damaged hair.

  It is also an object of the present invention to provide a method for using a formulation for repairing and / or strengthening hair after and / or during coloration or wave permanent processing.

  It is also an object of the present invention to provide multiple formulations and methods of using these formulations to repair and / or strengthen the hair after the reduction treatment.

  It is also an object of the present invention to provide a plurality of formulations that repair and / or strengthen keratin in hair, skin or nails by natural abrasion or natural aging, and methods for using these formulations. .

  Disclosed are formulations, kits and methods for repairing hair that has been cut during hair coloring or wave permanent processing. The formulation provides similar benefits when used in a variety of coloring chemistry processes such as bleaching, highlighting, lowlighting and slightly persistent, semi-persistent and persistent coloring. Also provided is an improved method of hair styling, such as hair wave perm and hair curl treatment. The formulation can be applied after shampooing or daily, once a week, twice a week, every other week, once a month, every other month or less frequently. The formulation is preferably applied once a month to achieve the desired result.

  In conventional methods of hair wave perm, hair curl or straightening treatment, hydrogen peroxide is used after the reduction treatment. The process typically takes about 3 days to complete. The methods disclosed herein use a plurality of active agents to repair the hair; these active agents are washed from the individual's hair during the same day that they are applied to the hair. Hair treated with the formulations disclosed herein under the same conditions, such as temperature and moisture, takes longer to return to its previous state compared to the same hair treated with hydrogen peroxide.

式中、Ｚはリンカーであるか、または存在せず；
ｍ及びｎは、各々独立して０〜６から選択される整数であり、ｍ＋ｎの合計が２以上であり；
Ｂはチオールなどの求核剤との共有結合を形成することが可能な官能基であり；
Ａはイオン化性官能基である
を有する活性剤を含む調合物を毛髪に塗布すること
を含む前記方法。
（項目２）
Ｂは独立して以下の式：

式中、Ｒは独立して水素、Ｃ_１‐６アルキル基、アリール基またはイオン化性官能基から成る群より選択され；
Ｚ’は酸素（Ｏ）、ＮＨであるか、または存在せず、Ｇは炭素（Ｃ）であり、ｇは１であり、またはＧは硫黄（Ｓ）であり、ｇは２である；
から成る群より選択され、また
Ａは独立して：‐ＣＯＯＨ、‐ＳＯ_３Ｈ、‐ＰＯ_３Ｈ_２及び‐Ｎ（Ｒ^１）_２、‐Ｎ（Ｒ^１）_３から成る群より選択し；式中、Ｒ^１は独立して、水素、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、ヘテロシクロアルキル及びヘテロアリール基から成る群より選択され；式中、各Ｒ^１は独立して、非置換であるか、または１つ以上の置換基で置換されている、項目１に記載の方法。
（項目３）
前記リンカーＺはアルキル基、アルケニル基、シクロアルキル基、シクロアルケニル基、アリール基、ヘテロシクロアルキル基またはヘテロアリール基であり、
ここではアルキル、アルケニル、シクロアルキル、シクロアルケニル、アリール、ヘテロシクロアルキルもしくはヘテロアリール基またはポリマーは非置換であるか、またはハロゲン、シアノ、アルコキシ、アルキル、アルケニル、シクロアルキル、シクロアルケニル、アリール、ヘテロシクロアルキル、ヘテロアリール、アミン、ヒドロキシ、オキソ、ホルミル、アシル、カルボン酸（‐ＣＯＯＨ）、‐Ｃ（Ｏ）Ｒ^１、‐Ｃ（Ｏ）ＯＲ^１、（‐ＣＯＯ^‐）、第一級アミド（例えば‐ＣＯＮＨ_２）、第二級アミド（例えば‐ＣＯＮＨＲ^１）、‐Ｃ（Ｏ）ＮＲ^１Ｒ^２、‐ＮＲ^１Ｒ^２、‐ＮＲ^１Ｓ（Ｏ）_２Ｒ^２、‐ＮＲ^１Ｃ（Ｏ）Ｒ^２、‐Ｓ（Ｏ）_２Ｒ^２、‐ＳＲ^１、‐Ｓ（Ｏ）_２ＮＲ^１Ｒ^２、‐ＳＯＲ^１または‐ＳＯＯＲ^１で１回以上置換しており；
式中、Ｒ^１及びＲ^２はそれぞれ独立して、水素、アルキル基、アルケニル基、アルキニル基、シクロアルキル基、アリール基、ヘテロシクロアルキル基及びヘテロアリール基から成る群より選択され、Ｒ^１及びＲ^２の各々は独立して非置換であるか、または１つ以上の置換基で置換されている、項目１または２のいずれか１項に記載の方法。
（項目４）
前記リンカーＺはＣ_１‐４アルキル基である、項目１〜３のいずれか１項に記載の方法。
（項目５）
前記アルキル基は、アルキル炭化水素主鎖の１個以上の炭素上で水素に取って代わる１つ以上の置換基で置換されるか、もしくは炭化水素の炭素主鎖内の１個以上のヘテロ原子で置換されるか、またはこれらの組合せで置換され、また
前記置換基はオキソ、ヒドロキシル、カルボキシル、アミド及びアミノ基から成る群より選択される、項目４に記載の方法。
（項目６）
毛髪中のジスルフィド結合を還元して遊離チオール基を生成することが可能な還元剤を含む第１調合物を塗付する工程が更に含まれ、
前記工程は工程（ａ）に先立って実行する、先行項目のいずれか１項に記載の方法。
（項目７）
前記還元剤は、チオグリコール酸ならびにその誘導体塩及びエステル、チオ乳酸ならびにその誘導体塩及びエステル、システイン及びその誘導体、システアミン及びその誘導体、無機亜硫酸塩、メタ重亜硫酸ナトリウム、他の無機重亜硫酸塩、ジチオスレイトール、ジチオエリスリトール、有機ホスフィン、更に日本製の縮毛矯正剤から成る群より選択される、項目６に記載の方法。
（項目８）
更に、工程（ａ）の前に、またはそれと同時に、
毛髪着色剤、及び毛髪中のジスルフィド結合を還元して遊離チオール基を生成することが可能な還元剤を含む着色調合物を毛髪に塗布すること
を含む項目１〜５のいずれか１項に記載の方法。
（項目９）
工程（ａ）の前に前記着色調合物を毛髪に塗布する、項目８に記載の方法。
（項目１０）
更に、工程（ａ）の前に、またはそれと同時に、毛髪を脱色し、遊離チオール基を生成するブリーチ処理剤を含むブリーチ処理調合物を毛髪に塗布することを含む項目１〜５のいずれか１項に記載の方法。
（項目１１）
工程（ａ）の前に前記ブリーチ処理調合物を毛髪に塗布する、項目１０に記載の方法。（項目１２）
前記調合物は更に、水、界面活性剤、ビタミン、天然エキス、防腐剤、キレート剤、香料、防腐剤、酸化防止剤、タンパク質、アミノ酸、保湿剤、芳香剤、軟化剤、浸透剤、増粘剤、粘度調整剤、毛髪固定剤、フィルム形成剤、乳化剤、不透明化剤、噴霧剤、液体ビヒクル、担体、塩、ｐＨ調整剤、中和剤、緩衝剤、毛髪コンディショニング剤、帯電防止剤、縮毛防止剤、ふけ防止剤及びこれらの組み合わせから成る群より選択される１種以上の薬学的に許容可能な賦形剤を含む、先行項目のいずれか１項に記載の方法。
（項目１３）
前記活性剤は前記調合物に対して約０．０１重量％〜約１０重量％の範囲の量である、先行項目のいずれか１項に記載の方法。
（項目１４）
前記活性剤は前記調合物に対して約０．５〜３重量％の範囲の量である、先行項目のいずれか１項に記載の方法。
（項目１５）
前記１種以上の賦形剤は前記調合物に対して約５０重量％〜約９０重量％の範囲の量である、先行項目のいずれか１項に記載の方法。
（項目１６）
前記調合物はゲル、クリーム、ローション、シャンプーまたはコンディショナーの形態である、先行項目のいずれか１項に記載の方法。
（項目１７）
工程（ａ）を１回以上繰り返す、先行項目のいずれか１項に記載の方法。
（項目１８）
更に：
（ｂ）毛髪をすすぎ、シャンプーで洗浄し、及び／あるいはコンディショニングすること
を含み、この工程（ｂ）は工程（ａ）の次に行う、先行項目のいずれか１項に記載の方法。
（項目１９）
工程（ｂ）は工程（ａ）の約１０分後に行う、項目１８に記載の方法。
（項目２０）
前記毛髪着色剤はハイライト処理剤、持続性着色剤、半持続性着色剤、及びやや持続性着色剤から成る群より選択される、項目８または９に記載の方法。
（項目２１）
前記活性剤は以下の式：

及びこれらの単塩から成る群より選択される、先行項目のいずれか１項に記載の方法。
（項目２２）
キットであって、
（ａ）毛髪着色剤、及び毛髪中のジスルフィド結合を還元して遊離チオール基を生成することが可能な還元剤を含む第１調合物、ならびに
（ｂ）以下の式：

式中、Ｚはリンカーであるか、または存在せず；
ｍ及びｎは各々独立して０〜６から選択される整数であり、また
ここではｍ＋ｎの合計は２以上であり；
Ｂはチオールなどの求核剤との共有結合を形成することが可能な官能基であり；
Ａはイオン化性官能基である
を有する活性剤を含む第２調合物
を備える前記キット。
（項目２３）
更にシャンプー、コンディショナー、使用説明書、顕色剤、グローブまたはこれらの組合せを備える項目２２に記載のキット。
（項目２４）
毛髪処理方法であって：
（ａ）以下の式：

式中、Ｚはリンカーであるか、または存在せず；
ｍ及びｎは各々独立して０〜６から選択される整数であり、ｍ＋ｎの合計は２以上であり；
Ｂはチオールなどの求核剤との共有結合を形成することが可能な官能基であり；
Ａはイオン化性官能基であり；また
Ｃはイオン基、ならびにチオールなどの求核剤との共有結合を形成することが可能な官能基を含み、イオン化性基Ａの電荷と反対の電荷を有し、Ｃ及びＡの電荷の合計がゼロになるようにｏは独立して０〜６から選択される整数値である
を有する活性剤を含む調合物を毛髪に塗布すること
を含む前記方法。
（項目２５）
Ｂは独立して以下の式：

式中、Ｒは独立して水素、Ｃ_１‐６アルキル基、アリール基またはイオン化性官能基から成る群より選択され；
Ｚ’は酸素（Ｏ）、ＮＨであるか、または存在せず、Ｇは炭素（Ｃ）であり、ｇは１であり、またはＧは硫黄（Ｓ）であり、ｇは２である；
から成る群より選択され、また
Ａは独立して‐ＣＯＯＨ、‐ＳＯ_３Ｈ、‐ＰＯ_３Ｈ_２及び‐Ｎ（Ｒ^１）_２、‐Ｎ（Ｒ^１）_３から成る群より選択され；式中、Ｒ^１は独立して、水素、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、ヘテロシクロアルキル及びヘテロアリール基から成る群より選択され；式中、各Ｒ^１は独立して、非置換であるか、または１つ以上の置換基で置換されている、項目２４に記載の方法。
（項目２６）
前記リンカーＺはアルキル基、アルケニル基、シクロアルキル基、シクロアルケニル基、アリール基、ヘテロシクロアルキル基、ヘテロアリール基またはポリマーであり、
ここではアルキル、アルケニル、シクロアルキル、シクロアルケニル、アリール、ヘテロシクロアルキルもしくはヘテロアリール基またはポリマーは非置換であるか、またはハロゲン、シアノ、アルコキシ、アルキル、アルケニル、シクロアルキル、シクロアルケニル、アリール、ヘテロシクロアルキル、ヘテロアリール、アミン、ヒドロキシ、オキソ、ホルミル、アシル、カルボン酸（‐ＣＯＯＨ）、‐Ｃ（Ｏ）Ｒ^１、‐Ｃ（Ｏ）ＯＲ^１、（‐ＣＯＯ^‐）、第一級アミド（例えば‐ＣＯＮＨ_２）、第二級アミド（例えば‐ＣＯＮＨＲ^１）、‐Ｃ（Ｏ）ＮＲ^１Ｒ^２、‐ＮＲ^１Ｒ^２、‐ＮＲ^１Ｓ（Ｏ）_２Ｒ^２、‐ＮＲ^１Ｃ（Ｏ）Ｒ^２、‐Ｓ（Ｏ）_２Ｒ^２、‐ＳＲ^１、‐Ｓ（Ｏ）_２ＮＲ^１Ｒ^２、‐ＳＯＲ^１または‐ＳＯＯＲ^１で１回以上置換しており、
式中、Ｒ^１及びＲ^２はそれぞれ独立して、水素、アルキル基、アルケニル基、アルキニル基、シクロアルキル基、アリール基、ヘテロシクロアルキル及びヘテロアリール基から成る群より選択され、式中、Ｒ^１及びＲ^２の各々は独立して非置換であるか、または１つ以上の置換基で置換されている、項目２４または２５に記載の方法。
（項目２７）
前記リンカーＺはＣ_１‐４アルキル基である、項目２４〜２６のいずれか１項に記載の方法。
（項目２８）
前記アルキル基は、アルキル炭化水素主鎖の１個以上の炭素上で水素に取って代わる１つ以上の置換基で置換されるか、もしくは炭化水素の炭素主鎖内の１個以上のヘテロ原子で置換されるか、またはこれらの組合せで置換され、また
前記置換基はオキソ、ヒドロキシル、カルボキシル、アミド及びアミノ基から成る群より選択される、項目２７に記載の方法。
（項目２９）
前記活性剤は：

である、項目２４〜２８のいずれか１項に記載の方法。 The formulations disclosed herein contain one or more multifunctional compounds. The multifunctional compound includes at least one ionizable functional group capable of forming an ionic bond, and the multifunctional compound also includes at least one functional group capable of forming a covalent bond with the thiol group. In some embodiments, the multifunctional compound includes at least two ionizable groups. Optionally, the formulation is applied simultaneously with hair coloring or wave permanent treatment. Alternatively, the preparation may be applied to damaged hair after hair coloring or wave permanent treatment. For example, the formulation is applied within a week after hair has been treated and / or damaged, preferably within 3 days, more preferably within 2 days, most preferably immediately after application of the coloring or wave permanent treatment. It is possible.
For example, the present invention provides the following items.
(Item 1)
A hair treatment method comprising:
(A) The following formula:

Where Z is a linker or absent;
m and n are each independently an integer selected from 0 to 6, and the sum of m + n is 2 or more;
B is a functional group capable of forming a covalent bond with a nucleophile such as a thiol;
A method as described above, comprising applying to the hair a formulation comprising an active agent wherein A is an ionizable functional group.
(Item 2)
B is independently the following formula:

Wherein R is independently selected from the group consisting of hydrogen, a C _1-6 alkyl group, an aryl group, or an ionizable functional group;
Z ′ is oxygen (O), NH or absent, G is carbon (C), g is 1, or G is sulfur (S), g is 2;
And A is independently selected from the group consisting of: —COOH, —SO ₃ H, —PO ₃ H ₂ and —N (R ¹ ) ₂ , —N (R ¹ ) ₃ ; Wherein R ¹ is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl and heteroaryl groups; wherein each R ¹ is independently unsubstituted Or the method of item 1, wherein the method is substituted with one or more substituents.
(Item 3)
The linker Z is an alkyl group, an alkenyl group, a cycloalkyl group, a cycloalkenyl group, an aryl group, a heterocycloalkyl group, or a heteroaryl group,
Where an alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl or heteroaryl group or polymer is unsubstituted or halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, hetero Cycloalkyl, heteroaryl, amine, hydroxy, oxo, formyl, acyl, carboxylic acid (—COOH), —C (O) R ¹ , —C (O) OR ¹ , (—COO ⁻ ), primary amide ( For example, —CONH ₂ ), secondary amide (eg, —CONHR ¹ ), —C (O) NR ¹ R ² , —NR ¹ R ² , —NR ¹ S (O) ₂ R ² , —NR ¹ C (O ^{_{) R 2, -S (O)}} 2 R 2, -SR 1, -S (O) 2 NR 1 R 2, -SOR 1 or - It has been substituted one or more times in the OOR ^1;
In the formula, R ¹ and R ² are each independently hydrogen, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, selected from the group consisting of heterocycloalkyl and heteroaryl groups, R ¹ and ^3. The method of any one of items 1 or ² , wherein each R ² is independently unsubstituted or substituted with one or more substituents.
(Item 4)
4. The method according to any one of items 1 to 3, wherein the linker Z is a C _1-4 alkyl group.
(Item 5)
The alkyl group is substituted with one or more substituents that replace hydrogen on one or more carbons of the alkyl hydrocarbon backbone, or one or more heteroatoms in the hydrocarbon carbon backbone. The method according to item 4, wherein the substituent is selected from the group consisting of oxo, hydroxyl, carboxyl, amide and amino groups.
(Item 6)
Further comprising applying a first formulation comprising a reducing agent capable of reducing disulfide bonds in the hair to produce free thiol groups;
The method according to any one of the preceding items, wherein the step is performed prior to the step (a).
(Item 7)
The reducing agent includes thioglycolic acid and its derivative salts and esters, thiolactic acid and its derivative salts and esters, cysteine and its derivatives, cysteamine and its derivatives, inorganic sulfite, sodium metabisulfite, other inorganic bisulfites, Item 7. The method according to Item 6, selected from the group consisting of dithiothreitol, dithioerythritol, organic phosphine, and a hair straightener made in Japan.
(Item 8)
Furthermore, before or simultaneously with step (a),
Item 6. Any one of Items 1 to 5, comprising applying to the hair a coloring composition comprising a hair coloring agent and a reducing agent capable of reducing a disulfide bond in the hair to produce a free thiol group. the method of.
(Item 9)
9. A method according to item 8, wherein the colored preparation is applied to the hair before step (a).
(Item 10)
Further, any one of items 1-5, comprising applying to the hair a bleaching formulation comprising a bleaching agent that decolorizes the hair and generates free thiol groups prior to or simultaneously with step (a). The method according to item.
(Item 11)
11. A method according to item 10, wherein the bleach treatment formulation is applied to the hair before step (a). (Item 12)
The formulation further comprises water, surfactants, vitamins, natural extracts, preservatives, chelating agents, fragrances, preservatives, antioxidants, proteins, amino acids, humectants, fragrances, softeners, penetrants, thickeners. Agent, viscosity modifier, hair fixative, film forming agent, emulsifier, opacifier, spray, liquid vehicle, carrier, salt, pH adjuster, neutralizer, buffer, hair conditioning agent, antistatic agent, shrinkage The method according to any one of the preceding items, comprising one or more pharmaceutically acceptable excipients selected from the group consisting of anti-hair agents, anti-dandruff agents and combinations thereof.
(Item 13)
A method according to any preceding item, wherein the active agent is in an amount ranging from about 0.01% to about 10% by weight relative to the formulation.
(Item 14)
The method according to any one of the preceding items, wherein the active agent is in an amount ranging from about 0.5 to 3% by weight relative to the formulation.
(Item 15)
The method of any preceding item, wherein the one or more excipients is in an amount ranging from about 50% to about 90% by weight relative to the formulation.
(Item 16)
A method according to any one of the preceding items, wherein the formulation is in the form of a gel, cream, lotion, shampoo or conditioner.
(Item 17)
The method according to any one of the preceding items, wherein step (a) is repeated one or more times.
(Item 18)
In addition:
(B) A method according to any one of the preceding items, comprising rinsing, shampooing and / or conditioning the hair, wherein step (b) follows step (a).
(Item 19)
Item 19. The method according to Item 18, wherein step (b) is performed about 10 minutes after step (a).
(Item 20)
10. A method according to item 8 or 9, wherein the hair colorant is selected from the group consisting of highlight treatments, persistent colorants, semi-persistent colorants, and slightly persistent colorants.
(Item 21)
The activator has the following formula:

And the method according to any one of the preceding items selected from the group consisting of these simple salts.
(Item 22)
A kit,
(A) a first formulation comprising a hair colorant and a reducing agent capable of reducing a disulfide bond in the hair to produce a free thiol group; and (b) the following formula:

Where Z is a linker or absent;
m and n are each independently an integer selected from 0 to 6, and here, the sum of m + n is 2 or more;
B is a functional group capable of forming a covalent bond with a nucleophile such as a thiol;
Said kit comprising a second formulation comprising an activator having A is an ionizable functional group.
(Item 23)
The kit according to item 22, further comprising a shampoo, a conditioner, instructions for use, a developer, a glove, or a combination thereof.
(Item 24)
A hair treatment method comprising:
(A) The following formula:

Where Z is a linker or absent;
m and n are each independently an integer selected from 0 to 6, and the sum of m + n is 2 or more;
B is a functional group capable of forming a covalent bond with a nucleophile such as a thiol;
A is an ionizable functional group; and C contains an ionic group as well as a functional group capable of forming a covalent bond with a nucleophile such as a thiol and has a charge opposite to that of the ionizable group A. And wherein o is an integer value independently selected from 0 to 6 so that the sum of the charges of C and A is zero, said method comprising applying to the hair a formulation comprising an active agent having:
(Item 25)
B is independently the following formula:

Wherein R is independently selected from the group consisting of hydrogen, a C _1-6 alkyl group, an aryl group, or an ionizable functional group;
Z ′ is oxygen (O), NH or absent, G is carbon (C), g is 1, or G is sulfur (S), g is 2;
And A is independently selected from the group consisting of —COOH, —SO ₃ H, —PO ₃ H ₂ and —N (R ¹ ) ₂ , —N (R ¹ ) ₃ ; In which R ¹ is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl and heteroaryl groups; wherein each R ¹ is independently unsubstituted 25. A method according to item 24, wherein the method is substituted with one or more substituents.
(Item 26)
The linker Z is an alkyl group, alkenyl group, cycloalkyl group, cycloalkenyl group, aryl group, heterocycloalkyl group, heteroaryl group or polymer,
Where an alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl or heteroaryl group or polymer is unsubstituted or halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, hetero Cycloalkyl, heteroaryl, amine, hydroxy, oxo, formyl, acyl, carboxylic acid (—COOH), —C (O) R ¹ , —C (O) OR ¹ , (—COO ⁻ ), primary amide ( For example, —CONH ₂ ), secondary amide (eg, —CONHR ¹ ), —C (O) NR ¹ R ² , —NR ¹ R ² , —NR ¹ S (O) ₂ R ² , —NR ¹ C (O ^{_{) R 2, -S (O)}} 2 R 2, -SR 1, -S (O) 2 NR 1 R 2, -SOR 1 or - Has been substituted one or more times in the OOR ^1,
Wherein R ¹ and R ² are each independently selected from the group consisting of hydrogen, alkyl groups, alkenyl groups, alkynyl groups, cycloalkyl groups, aryl groups, heterocycloalkyl and heteroaryl groups, wherein R 1 26. A method according to item 24 or 25, wherein each of ¹ and R ² is independently unsubstituted or substituted with one or more substituents.
(Item 27)
27. A method according to any one of items 24-26, wherein the linker Z is a C _1-4 alkyl group.
(Item 28)
The alkyl group is substituted with one or more substituents that replace hydrogen on one or more carbons of the alkyl hydrocarbon backbone, or one or more heteroatoms in the hydrocarbon carbon backbone. 28. The method according to item 27, wherein the substituent is selected from the group consisting of oxo, hydroxyl, carboxyl, amide and amino groups.
(Item 29)
The active agent is:

29. A method according to any one of items 24-28.

I. Definitions The term “hair” refers to one or more hair as well as natural hair components such as oil from the body. Hair also refers to virgin hair or treated hair, such as hair that has been exposed to hair waves or straightening treatment formulations.

  “Pharmaceutically acceptable” and “cosmetically acceptable” are used interchangeably and refer to excessive toxicity, irritation, allergic reactions, or other problems or equivalent to a reasonable benefit / risk ratio. Refers to those compounds, materials and / or formulations suitable for use in contact with human and animal tissue within the scope of reasonable medical judgment without complex factors. More specifically, “pharmaceutically acceptable” refers to a material, compound or formulation suitable for use in contact with the skin, scalp or hair. Pharmaceutically acceptable materials are known to those skilled in the art.

  As used herein, “shampoo” refers to a liquid or semi-solid formulation that is applied to the hair, generally containing a detergent or soap for washing the hair.

  As used herein, a “conditioner” generally refers to a formulation (eg, liquid, cream, lotion, gel, etc.) that is applied to the hair to soften the hair, smooth the hair, and / or change the gloss of the hair. Semi-solid).

  “Analog” and “derivative” are used interchangeably and have the same core as the parent compound, but the bond order and the presence or absence of one or more atoms and / or atomic groups or combinations thereof are Refers to different compounds. Derivatives may differ from the parent compound in one or more substituents present in the core, which may include, for example, one or more atoms, functional groups or substructures. In general, a derivative can be formed at least theoretically from a parent compound through chemical and / or physical processes.

  “Electrophilic group” or “electrophilic moiety” are used interchangeably and refer to one or more functional groups or moieties that have an affinity for or withdraw an electron.

  “Nucleophilic group” or “nucleophilic moiety” are used interchangeably and refer to one or more functional groups or moieties that are rich in electrons and capable of reacting with an electrophilic group.

  As used herein, a “Michael acceptor” is a type of electrophilic group or moiety that participates in a nucleophilic addition reaction. The Michael acceptor can be or include an α, β-unsaturated carbonyl containing group or moiety such as a ketone. Other Michael acceptors include π bonds such as double or triple bonds conjugated with other π bonds including electron withdrawing groups such as nitro, nitrile and carboxylic acid groups.

  As used herein, “carboxylic acid” refers to a —COOH group. Unless otherwise specified, the term carboxylic acid encompasses both free acids and carboxylates.

“Alkyl” as used herein refers to a radical of a saturated or unsaturated aliphatic group, including straight chain alkyl, alkenyl or alkynyl group, branched chain alkyl, alkenyl or alkynyl group, cycloalkyl, cycloalkenyl. Or cycloalkynyl (alicyclic) groups, alkyl-substituted cycloalkyl, cycloalkenyl or cycloalkynyl groups, and cycloalkyl-substituted alkyl, alkenyl or alkynyl groups. Unless otherwise indicated, a straight chain or branched alkyl is ₃₀ carbon atoms or less in its main chain (eg, C ₁ -C ₃₀ for straight chain, C ₃ -C ₃₀ for branched chain), Preferably it has no more than 20 carbon atoms, more preferably no more than 12 carbon atoms, and most preferably no more than 8 carbon atoms. In some embodiments, the chain has 1 to 6 carbons. Likewise, preferred cycloalkyls have from 3-10 carbon atoms in their ring structure, and more preferably have 5, 6 or 7 carbons in the ring structure. The above range includes all values between the minimum and maximum values.

  The term “alkyl” includes both “unsubstituted alkyl” and “substituted alkyl,” the latter having an alkyl moiety having one or more substituents that replace hydrogen on one or more carbons of the hydrocarbon backbone. Point to. Such substituents include halogen, hydroxyl, carbonyl (such as carboxyl, alkoxycarbonyl, formyl or acyl), thiocarbonyl (such as thioester, thioacetate or thioformate), alkoxyl, phosphoryl, phosphate, phosphonate, phosphinate, amino, amide , Amidine, imine, cyano, nitro, azide, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamide, sulfonyl, heterocyclyl, aralkyl, or aromatic or heteroaromatic moieties, including but not limited to Absent.

  Unless otherwise specified, the term “lower alkyl” as used herein means an alkyl group as defined above, provided that the alkyl group has 1-10 carbons in the main chain structure, More preferably it has 1 to 6 carbon atoms. Similarly, “lower alkenyl” and “lower alkynyl” have similar chain lengths. Preferred alkyl groups are lower alkyl.

  Alkyl groups may also contain one or more heteroatoms in the carbon backbone. Examples include oxygen, nitrogen, sulfur and combinations thereof. In certain embodiments, the alkyl group contains 1-4 heteroatoms.

As used herein, “alkenyl” and “alkynyl” are one or more doubles that are similar in length (eg, C ₂ -C ₃₀ ) to the alkyl group described above and that can be substituted for the alkyl group. Or it refers to an unsaturated aliphatic group containing a triple bond.

“Aryl” as used herein refers to 5-, 6- and 7-membered aromatic rings. The ring may be a carbocycle, heterocycle, fused carbocycle, fused heterocycle, dicarbocycle or diheterocycle system and may optionally be substituted as described above for alkyl. As used herein and broadly defined, “Ar” includes 5-, 6-, and 7-membered monocyclic aromatic groups that may contain 0-4 heteroatoms. Examples include, but are not limited to, benzene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine. These aryl groups having heteroatoms in the ring structure may be referred to as “heteroaryl”, “aryl heterocycle” or “heteroaromatic”. Aromatic rings are at one or more ring positions and may be substituted as described above, for example, halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, alkoxyl, amino, nitro, sulfhydryl, imino, amide, phosphonate , Phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, sulfonamide, ketone, aldehyde, ester, heterocyclyl, aromatic or heteroaromatic moiety, can be substituted with --CF ₃ and --CN . The term “Ar” also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are in common with two adjacent rings (rings are “fused rings”), where In which at least one of the rings is an aromatic ring, for example the other cyclic ring may be a cycloalkyl, cycloalkenyl, cycloalkynyl, aryl and / or heterocycle, or both rings are aromatic. It is.

  “Alkylaryl” as used herein refers to an alkyl group substituted with an aryl group (eg, an aromatic or heteroaromatic group).

As used herein, “heterocycle” or “heterocyclic” includes carbon and 1-4 heteroatoms each selected from non-peroxygen oxygen, sulfur and N (Y), and Y Is absent or is H, O, (C _1-4 ) alkyl, phenyl or benzyl, optionally containing one or more double or triple bonds, optionally substituted with one or more substituents, Refers to a cyclic radical attached via a ring carbon or nitrogen of a monocyclic or bicyclic ring containing 3 to 10 ring atoms, preferably 5 to 6 ring atoms. The term “heterocycle” also includes substituted and unsubstituted heteroaryl rings. Examples of heterocycles include benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benz Isothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H, 6H-1,5,2-dithiazinyl, dihydrofuro [2,3-b] tetrahydrofuran, Furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl Isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2, 5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxyindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxatinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidonyl 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazo , Pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolidinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoxyl Nolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4 Examples include, but are not limited to, thiadiazolyl, thiantenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl and xanthenyl.

As used herein, “heteroaryl” includes 1, 2, 3, or 4 heteroatoms each selected from carbon and non-peroxygen oxygen, sulfur, and N (Y), and Y Refers to a monocyclic aromatic ring containing 5 or 6 ring atoms that is absent or is H, O, (C ₁ -C ₈ ) alkyl, phenyl or benzyl. Non-limiting examples of heteroaryl groups include furyl, imidazolyl, triazolyl, triazinyl, oxazoyl, isoxazoyl, thiazolyl, isothiazoyl, pyrazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridyl (or its N-oxide), thienyl, pyrimidinyl (or (N-oxide thereof), indolyl, isoquinolyl (or N-oxide thereof), quinolyl (or N-oxide thereof) and the like. The term “heteroaryl” is derived from an ortho-fused bicyclic heterocycle of about 8-10 ring atoms derived therefrom, in particular a benz-derivative, or a propylene, trimethylene or tetramethylene diradical by fusing it thereto. Derivative radicals may be included. Examples of heteroaryl include furyl, imidazolyl, triazolyl, triazinyl, oxazoyl, isoxazoyl, thiazolyl, isothiazoyl, pyrazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridyl (or its N-oxide), thienyl, pyrimidinyl (or its N-oxide) , Indolyl, isoquinolyl (or its N-oxide), quinolyl (or its N-oxide), and the like, but are not limited thereto.

  As used herein, “halogen” refers to fluorine, chlorine, bromine or iodine.

The term “substituted” as used herein refers to all permissible substituents of the compounds described herein. In the broadest sense, acceptable substituents include acyclic and cyclic, branched and unbranched, carbocycles and heterocycles, aromatic and non-aromatic substituents of organic compounds. Exemplary substituents include halogens, hydroxyl groups, or any other organic group containing any number of carbon atoms, preferably 1 to 14 carbon atoms, optionally linear, branched or cyclic Examples include, but are not limited to, one or more heteroatoms such as oxygen, sulfur or nitrogen groups in structural form. Exemplary substituents include alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halo, hydroxyl, alkoxy, substituted alkoxy, phenoxy , Substituted phenoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amide, substituted amide , sulfonyl, substituted sulfonyl, sulfonic acid, phosphoryl, substituted phosphoryl, phosphonyl, substituted phosphonyl, polyaryl, substituted _polyaryl, C 3 _{-C 20} ring, substituted ₃ -C ₂₀ ring, a heterocyclic ring, substituted heterocyclic, amino acid, include peptides and polypeptides groups.

  Heteroatoms such as nitrogen may include hydrogen substituents and / or any acceptable substituent of the organic compounds described herein that satisfy the valence of the heteroatom. "Substituted" or "substituted" is a compound in which such substitution is consistent with the substituent atom and the acceptable valence of the substituent and is not naturally converted by rearrangement, cyclization, elimination, etc. It is understood that contains the implicit condition that occurs by substitution.

  As used herein, “polymer” refers to a molecule comprising more than 10 monomer units.

  As used herein, “water-soluble” generally means that at least 50, 75, 100, 125, 150, 200, 225 or 250 g can be dissolved in 1 liter of water at 25 ° C.

II. Formulations The formulations and methods disclosed herein relate to the treatment of keratin in hair, skin or nails. In one embodiment, the method relates to strengthening and / or repairing the hair after applying a color treatment or after or during a wave perm treatment. The formulation can also reduce or prevent hair damage due to hair coloring and / or bleaching processes.

A. Formulations Formulations include one or more multifunctional compounds (also referred to herein as “active agents”).

  Active agents are considered safe and effective for human hair and / or scalp, and do not cause adverse biological side effects such as burning, itching and / or redness or similar adverse reactions Can be combined with one or more pharmaceutically acceptable carriers and / or excipients that can be administered to the patient. The formulation may further comprise excipients that bring the pH of the formulation to neutral, or from about pH 3 to about pH 12, preferably from pH 5 to pH 8.

  The active agent is typically about 0.01% to about 50% by weight of the formulation, preferably about 1% to about 25%, more preferably about 1% to about 15% by weight of the formulation. %, Most preferably in an amount ranging from about 1% to about 10% by weight. Typically, the active agent may be present in an amount ranging from about 0.5 to about 3% by weight of the formulation, or from about 1 to about 3% by weight of the formulation.

  The active agent is at a pH of 6-8, a temperature of about 25-30 ° C, preferably about 25 ° C, for a period of at least 2, 3, 4, 5, 6, 8, 9, 10, 11 or 12 months or more. Stable in aqueous solution. As used herein with respect to shelf life, “stable” means that at least 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90 or 95% of the compound is present over a specified period of time. It means no change.

a. Activators An activator is a polyfunctional compound that may contain an ionic bond capable of forming a covalent bond with a thiol and an ionizable functional group capable of forming a functional group. Suitable ionizable functional groups include, but are not limited to, acidic groups such as carboxylic acids, sulfonic acids and phosphonic acids, and basic groups such as amines. Suitable functional groups capable of forming a covalent bond with a thiol include, but are not limited to, Michael acceptors, alkyl halides or sulfonate esters.

を有してもよく、
式中、Ｚはリンカーであるか、または存在せず、ｍ及びｎは、ｍ＋ｎが少なくとも２であることを条件に、各々独立して０〜６から選択される整数であり、Ｂはチオールとの共有結合を形成することが可能な官能基であり、Ａはイオン化性官能基である。いくつかの実施形態では、イオン化性基Ａは独立して：‐ＣＯＯＨ、‐ＳＯ_３Ｈ、‐ＰＯ_３Ｈ_２及び‐Ｎ（Ｒ^１）_２から成る群より選択することが可能であり；式中、Ｒ^１は独立して、水素、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、ヘテロシクロアルキル及びヘテロアリール基から成る群より選択され；式中、各Ｒ^１は独立して、非置換であるか、または１つ以上の置換基で置換される。いくつかの他の実施形態では、イオン化性基Ａは、‐Ｎ^＋（Ｒ^１）_３などのイオン基とすることが可能である。いくつかの好ましい実施形態では、各Ｒ^１は独立して、メチル、エチルまたはイソプロピル基から選択される。 The activator has the following formula I:

You may have
Wherein Z is a linker or absent, and m and n are each independently an integer selected from 0-6, provided that m + n is at least 2, and B is a thiol A is a functional group capable of forming a covalent bond, and A is an ionizable functional group. In some embodiments, the ionizable group A can be independently selected from the group consisting of: —COOH, —SO ₃ H, —PO ₃ H ₂ and —N (R ¹ ) ₂ ; In which R ¹ is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl and heteroaryl groups; wherein each R ¹ is independently unsubstituted Is or is substituted with one or more substituents. In some other embodiments, the ionizable group A can be an ionic group such as —N ⁺ (R ¹ ) ₃ . In some preferred embodiments, each R ¹ is independently selected from methyl, ethyl, or isopropyl groups.

に示す部分など、基Ｂとしてのチオール反応性官能基を含んでもよく、
式中、Ｒは独立して、水素、Ｃ_１‐６アルキル、アリールまたはイオン化性官能基から選択され；Ｚ’は酸素（Ｏ）、ＮＨであるか、または存在せず；Ｇは炭素（Ｃ）であり、ｇは１であり、またはＧは硫黄（Ｓ）であり、ｇは２である。 Exemplary active agents according to Formula I are, for example, the following moieties:

And may contain a thiol-reactive functional group as group B, such as
Wherein R is independently selected from hydrogen, C _1-6 alkyl, aryl or ionizable functional groups; Z ′ is oxygen (O), NH or absent; G is carbon (C ) And g is 1 or G is sulfur (S) and g is 2.

  When present, the linker Z can be or include an alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl or heteroaryl group. One or more carbon atoms in the alkyl, alkenyl, cycloalkyl, cycloalkenyl, and aryl groups can be substituted with a heteroatom, for example, to produce an ether or alkylamine-containing linker.

Linker Z is optional and may be substituted with one or more substituents which may be the same or different, including hydrogen, halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl , Heterocycloalkyl, heteroaryl, amine, hydroxy, oxo, formyl, acyl, carboxylic acid (—COOH), —C (O) R ¹ , —C (O) OR ¹ , carboxylate (—COO—), Primary amide (eg -CONH ₂ ), secondary amide (eg -CONHR ₁₁ ), -C (O) NR ¹ R ² , -NR ¹ R ² , -NR ¹ S (O) ₂ R ² ,- NR ¹ C (O) R ² , —S (O) ₂ R ² , —SR ¹ , and —S (O) ₂ NR ¹ R ² , a sulfinyl group (eg, —SOR ₁ ) and a sulfonyl group ( -SOOR ₁ ); wherein R ¹ and R ² may each independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl and heteroaryl; R ¹ And each of R ² is optionally independently halogen, hydroxyl, oxo, cyano, nitro, amino, alkylamino, dialkylamino, optionally alkyl substituted with one or more halogen or alkoxy or aryloxy, optionally Aryl substituted with one or more halogen or alkoxy or alkyl or trihaloalkyl, optionally heterocycloalkyl substituted with aryl or heteroaryl or oxo, or optionally substituted with hydroxyl, optionally substituted with hydroxyl Cycloalkyl, heteroaryl optionally substituted with one or more halogen or alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl and dialkylaminocarbonyl Substituted with one or more substituents selected from the group consisting of

In certain preferred embodiments, linker Z is a C _1-10 alkyl group that is unsubstituted or optionally substituted one or more times with oxo, hydroxyl, carboxyl, amide, or amino. Preferably, linker Z is a C _1-4 alkyl group. The alkyl group may be linear or branched. The alkyl group may be interrupted one or more times by a heteroatom selected from oxygen, sulfur and nitrogen. One example of such a dicarboxylic acid having a heteroatom interrupt is thiodipropionic acid. In other embodiments, the alkyl group may contain one or more double or triple bonds.

のうちの１つを有するか、またはこれらの構造の単塩である。 In some embodiments, the active agent of formula I has the following structure:

Or have a single salt of these structures.

を有してもよく、
式中、Ｚはリンカーであるか、または存在せず、ｍ及びｎは、ｍ＋ｎが少なくとも２であることを条件に、各々独立して０〜６から選択される整数であり、Ｂは、限定するものではないがチオールまたはアミン基などの求核剤との共有結合を形成することが可能な官能基であり、Ａは上述で定義したようなイオン化性官能基であり、Ｃはイオン基、ならびに、限定するものではないがチオールまたはアミン基などの求核剤との共有結合を形成することが可能で、イオン化性基Ａの電荷と反対の電荷を有する官能基を含む。基Ｃは、基Ａにイオン結合している（破線で示す）。イオン基Ｃでは、基Ｃ及びイオン化性基Ａの電荷の合計がゼロになるようにｏは独立して０〜６から選択される整数値である。いくつかの実施形態では、イオン化性基Ａは独立して：‐ＣＯＯＨ、‐ＳＯ_３Ｈ、‐ＰＯ_３Ｈ_２、及び‐Ｎ（Ｒ^１）_２から成る群より選択することが可能であり；式中、Ｒ^１は独立して、水素、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、ヘテロシクロアルキル及びヘテロアリール基から成る群より選択され；式中、各Ｒ^１は独立して、非置換であるか、または１つ以上の置換基で置換されている。いくつかの他の実施形態では、イオン化性基Ａは、‐Ｎ^＋（Ｒ^１）_３などのイオン基とすることが可能である。いくつかの好ましい実施形態では、各Ｒ^１は独立して、メチル、エチルまたはイソプロピル基から選択される。 In certain other embodiments, the active agent is of the following formula II:

You may have
Wherein Z is a linker or absent, and m and n are each independently an integer selected from 0 to 6, provided that m + n is at least 2, and B is a limitation A functional group capable of forming a covalent bond with a nucleophile, such as a thiol or amine group, A is an ionizable functional group as defined above, C is an ionic group, As well as, but not limited to, functional groups that can form covalent bonds with nucleophiles such as thiol or amine groups and have a charge opposite to that of the ionizable group A. The group C is ionically bonded to the group A (indicated by a broken line). In the ionic group C, o is an integer value independently selected from 0 to 6 so that the total charge of the group C and the ionizable group A becomes zero. In some embodiments, the ionizable group A can be independently selected from the group consisting of: —COOH, —SO ₃ H, —PO ₃ H ₂ , and —N (R ¹ ) ₂ ; Wherein R ¹ is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl and heteroaryl groups; wherein each R ¹ is independently unsubstituted Or is substituted with one or more substituents. In some other embodiments, the ionizable group A can be an ionic group such as —N ⁺ (R ¹ ) ₃ . In some preferred embodiments, each R ¹ is independently selected from methyl, ethyl, or isopropyl groups.

に示す部分などの基Ｂとしてのチオール反応性官能基を含んでもよく、
式中、Ｒは独立して、水素、Ｃ_１‐６アルキル、アリールまたはイオン化性官能基から選択され；Ｚ’は酸素（Ｏ）、ＮＨであるか、または存在せず；Ｇは炭素（Ｃ）であり、ｇは１であり、またはＧは硫黄（Ｓ）であり、ｇは２である。 Activators according to formula II are for example the following parts:

A thiol-reactive functional group as a group B such as the moiety shown in
Wherein R is independently selected from hydrogen, C _1-6 alkyl, aryl or ionizable functional groups; Z ′ is oxygen (O), NH or absent; G is carbon (C ) And g is 1 or G is sulfur (S) and g is 2.

  When present, the linker Z can be or include an alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl or heteroaryl group. One or more carbon atoms in the alkyl, alkenyl, cycloalkyl, cycloalkenyl, and aryl groups can be substituted with a heteroatom, for example, to produce an ether or alkylamine-containing linker.

Linker Z is optional and may be substituted with one or more substituents which may be the same or different, including hydrogen, halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl , Heterocycloalkyl, heteroaryl, amine, hydroxy, oxo, formyl, acyl, carboxylic acid (—COOH), —C (O) R ¹ , —C (O) OR ¹ , carboxylate (—COO—), Primary amide (eg -CONH ₂ ), secondary amide (eg -CONHR ¹ ), -C (O) NR ¹ R ² , -NR ¹ R ² , -NR ¹ S (O) ₂ R ² ,- NR ¹ C (O) R ² , —S (O) ₂ R ² , —SR ¹ , and —S (O) ₂ NR ¹ R ² , a sulfinyl group (eg, —SOR ₁ ) and a sulfonyl group (eg, -SOOR ¹ ); wherein R ¹ and R ² may each independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl; R ¹ And each of R ² is optionally independently halogen, hydroxyl, oxo, cyano, nitro, amino, alkylamino, dialkylamino, optionally substituted with one or more halogen or alkoxy or aryloxy, optionally Aryl substituted with one or more halogen or alkoxy or alkyl or trihaloalkyl, optionally heterocycloalkyl substituted with aryl or heteroaryl or oxo, or optionally substituted with hydroxyl, optionally substituted with hydroxyl The Cycloalkyl, heteroaryl optionally substituted with one or more halogen or alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl and dialkylaminocarbonyl Substituted with one or more substituents selected from the group consisting of

In certain preferred embodiments, linker Z is a C _1-10 alkyl group that is unsubstituted or optionally substituted one or more times with oxo, hydroxyl, carboxyl, amide, or amino. Preferably, linker Z is a C _1-4 alkyl group. The alkyl group may be linear or branched. The alkyl group may be interrupted one or more times by a heteroatom selected from oxygen, sulfur and nitrogen. One example of such a dicarboxylic acid having a heteroatom interrupt is thiodipropionic acid. In other embodiments, the alkyl group may contain one or more double or triple bonds.

  The group C is an ionic group ionically bonded to the ionizable group A, and also includes a Michael acceptor, a succinimidyl-containing group, a maleimide-containing group, an azlactone, a benzoxazinone derivative, a vinylsulfone, a vinylsulfoximine, a vinylsulfonate, and a vinylphosphonate , Benzoxazinone, isocyanate, epoxide, leaving group-containing electrophilic moiety, electrophilic thiol acceptor, acrylic or acrylate group, methacrylic or methacrylate group, styrene group, acrylamide group, methacrylamide group, maleate group, fumarate group, itaconate Group, vinyl ether group, allyl ether group, allyl ester group, vinyl ester group, sulfonate group, phosphonate group, sulfoxide group, sulfonamide group, sulfinimide group, sulfinamide , Comprising at least one thiol-reactive group selected from a sulfonic imidate group or sulfonimide amide group.

のうちの１つを有する。 In some embodiments, the active agent of formula II has the following structure:

One of them.

b. Excipients Formulations usually contain one or more cosmetically acceptable excipients. Cosmetically acceptable excipients include preservatives, antioxidants, chelating agents, sunscreen agents, vitamins, dyes, hair colorants, proteins, amino acids, plant extracts and other natural extracts, wetting agents, fragrances , Fragrances, oils, softeners, lubricants, butter, penetrants, thickeners, viscosity modifiers, polymers, resins, hair fixatives, film formers, surfactants, detergents, emulsifiers, opacifiers , Volatile oils, sprays, liquid vehicles, carriers, salts, pH adjusters (eg citric acid), neutralizers, buffers, hair conditioners, antistatic agents, anti-shrink agents, anti-dandruff agents, absorbents and these However, it is not limited to these.

  The formulations usually contain at least two cosmetically acceptable excipients. In some forms, the formulation includes an active agent, water, and optionally preservatives and / or fragrances.

  The formulation for treating the hair can be any suitable physical form. Suitable forms include, but are not limited to, low to moderately viscous liquids, lotions, emulsions, mousses, sprays, gels, creams, shampoos, conditioners and the like. Suitable excipients as listed above are included in or excluded from the hair care formulation depending on the form of use of the formulation (eg, hair spray, cream, conditioner or shampoo).

  Pharmaceutical excipients usually range from about 10% to about 99.99%, preferably from about 40% to about 90%, more preferably from about 80% to about 99% by weight of the formulation. Present in the amount of.

i. Surfactants Surfactants are surfactants that reduce the surface tension of water and allow the hair formulation to slide across or over the skin or hair. Surfactants also include detergents and soaps. Surfactants may be amphoteric, anionic or cationic. Suitable surfactants that may be used in the formulation include 3-aminopropane sulfonic acid, almond amide, almond amidopropyl betaine, oxidized almond amidopropylamine, hydrogenated aluminum tallow glutamate, aluminum lanolinate, amino sulfate Ethyl, aminopropyl lauryl glutamine, C _12-15 alkyl ammonium sulfate, C _12-15 pares ammonium sulphate, C _12-15 alkyl ammonium sulphate, C _9-10 ammonium perfluoroalkyl sulphonate, capryres ammonium sulphate, capryres-3 ammonium sulphate, monoglyceride ammonium sulphate, Ammonium sulfate, ammonium isothionate, ammonium cocoyl sarcosinate, ammonium cumene sulfonate, dimethicone copolio Ammonium sulfate, ammonium dodecylbenzenesulfonate, ammonium isostearate, ammonium laureth sulfate, ammonium laureth-12 sulfate, ammonium laureth-5 sulfate, ammonium laureth-6 carboxylate, laureth-7 ammonium sulfate, ammonium laureth-8 carboxylate, ammonium laureth-9 , Ammonium lauroyl sarcosinate, ammonium lauryl sulfate, ammonium lauryl sulfosuccinate, ammonium millesulphate, ammonium myristyl sulfate, ammonium nonoxynol-30, ammonium nonoxynol-4 sulfate, ammonium oleate, ammonium palm kernel, ammonium polyacrylate, ammonium stearate, ammonium tartrate , Kissi Ammonium sulfonate, amp-isostearoyl gelatin / keratin amino acid / lysine hydroxypropyltrimonium chloride, amp-isostearoyl hydrolyzed collagen, apricot oil PEG-6 ester, apricot amide, apricot amide propyl betaine, arachides-20, avocado amide, Avocadoamidopropyl betaine, babasamide, babasamidopropyl betaine, oxidized babasamidopropylamine, behenalkonium chloride, behenamide, behenamidopropyl betaine, behenamide oxide, sodium laureth sulfate, sodium lauryl sulfate, polyoxyether or ceteares-20 of lauryl alcohol, A combination thereof may be mentioned, but the invention is not limited to these.

  Suitable anionic surfactants include, but are not limited to, those containing carboxylic acid, sulfonic acid and sulfate ions. Examples of anionic surfactants include sodium, potassium, ammonium long-chain alkyl sulfonates, and alkylaryl sulfonates such as sodium dodecylbenzene sulfonate; sodium dialkylsulfosuccinates such as sodium dodecylbenzene sulfonate; bis- And sodium dialkylsulfosuccinates such as sodium (2-ethylthioxyl) -sulfosuccinate; and alkyl sulfates such as sodium lauryl sulfate. Cationic surfactants include, but are not limited to, quaternary ammonium compounds such as benzalkonium chloride, benzethonium chloride, cetrimonium bromide, stearyldimethylbenzylammonium chloride, polyoxyethylene and coconut amine. It is not something. Examples of nonionic surfactants include ethylene glycol monostearate, propylene glycol myristate, glyceryl monostearate, glyceryl stearate, polyglyceryl oleate-4, sorbitan acylate, sucrose acylate, PEG-150 laurate PEG-400 monolaurate, polyoxyethylene monolaurate, polysorbate, polyoxyethylene octyl phenyl ether, PEG-1000 cetyl ether, polyoxyethylene tridecyl ether, polypropylene glycol butyl ether, poloxamer (registered trademark) 401, stearoyl monoisopropanolamide And polyoxyethylene hydrogenated tallow amide. Examples of amphoteric surfactants include sodium N-dodecyl-β-alanine, sodium N-lauryl-β-iminodipropionate, myristoamphoacetate, lauryl betaine and lauryl sulfobetaine.

  More than one surfactant may be included in the formulation.

  Surfactants are optionally included in amounts ranging from about 0.1% to about 15% by weight of the formulation, preferably from about 1% to about 10% by weight of the formulation.

ii. Softener Softener refers to a material that protects against moisture and irritation, softens, smoothes, coats, lubricates, moisturizes, protects and / or cleanses the skin. Suitable softeners for use in the formulations include silicone compounds (eg, dimethicone, cyclomethicone, dimethicone copolyol, or a mixture of cyclopentasiloxane and dimethicone / vinyl dimethicone crosspolymer, cyclopentasiloxane polysilicone), sorbitol, Polyols such as glycerin, propylene glycol, ethylene glycol, polyethylene glycol, caprylyl glycol, polypropylene glycol, 1,3-butanediol, hexylene glycol, isoprene glycol, xylitol; ethyl hexyl palmitate; triglycerides such as caprylic acid / capric acid triglyceride And fatty acid esters such as cetearyl isononanoate or cetyl palmitate. It is not specified. In certain embodiments, the softening agent is dimethicone, amidodimethicone, dimethiconol, cyclopentasiloxane, PEG-7 dimethicone panthenyl potassium phosphate, or combinations thereof. More than one softener may be included in the formulation.

  Softeners are optionally included in amounts ranging from about 0.5% to about 15% by weight of the formulation, preferably from about 1% to about 10% by weight of the formulation.

iii. Emulsifier The formulation may also contain one or more emulsifiers. Suitable emulsifiers include copolymers of unsaturated esters and styrene sulfonate monomers, cetearyl alcohol, glyceryl esters, polyoxyethylene glycol ethers of cetearyl alcohol, stearic acid, polysorbate-20, ceteares-20, lecithin, stearin Examples include, but are not limited to, acid glycol, polysorbate-60, polysorbate-80, or combinations thereof. More than one emulsifier may be included in the formulation.

  The emulsifier is optionally included in an amount ranging from about 0.05% to 15% by weight of the formulation, preferably from about 0.1% to 10% by weight of the formulation.

iv. Preservatives One or more preservatives may be included in the formulation. Suitable preservatives include glycerin-containing compounds (eg glycerin, ethylhexyl glycerin or phenoxyethanol), benzyl alcohol, parabens (such as methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben), sodium benzoate, ethylenediaminetetraacetic acid (EDTA ), Potassium sorbate, and / or grapefruit seed extract, or combinations thereof, but are not limited thereto. More than one preservative may be included in the formulation. Other preservatives are known in the cosmetics industry and include salicylic acid, DMDM hydantoin, formaldehyde, chlorphenism, triclosan, imidazolidinyl urea, diazolidinyl urea, sorbic acid, methylisothiazolinone, sodium dehydroacetate, dehydroacetic acid, quaternium -15, stearalkonium chloride, pyrithione zinc, sodium metabisulfite, 2-bromo-2-nitropropane, chlorhexidine digluconate, polyaminopropyl biguanide, benzalkonium chloride, sodium sulfite, sodium salicylate, citric acid, neem oil, Examples include essential oil (various), lactic acid and vitamin E (tocopherol).

  Preservatives are optionally included in amounts ranging from about 0.1% to about 5% by weight of the formulation, preferably from about 0.3% to about 3% by weight of the formulation. The formulation is preferably paraben free.

v. Conditioning agents One or more conditioning agents may be included in the formulation. Suitable conditioning agents include silicone materials (eg silicone quaternium-8), panthenol, hydrolyzed wheat and / or soy protein, amino acids (eg wheat amino acids), rice bran wax, meadow foam seed oil, mango seed oil , Grape seed oil, jojoba seed oil, sweet almond oil, hydroxyethyl behenamidopropyl dimonium chloride, aloe leaf extract, aloe vera leaf juice, phytantriol, panthenol, retinyl palmitate, behentrimonium methosulfate, cyclopentasiloxane , Quaternium-91, stearamidopropyldimethylamine, and combinations thereof, but are not limited thereto.

  The conditioning agent (s) is optional and is in an amount ranging from about 0.1% to about 5% by weight of the formulation, preferably from about 0.3% to about 3% by weight of the formulation. Is included.

vi. Diluent As used herein, diluent refers to the substance or substances that dilute the active agent. Water is a preferred diluent. Formulations typically contain more than 1 (weight) percent water, preferably more than 5 (weight) percent water, more preferably more than 50 (weight) percent water, most preferably more than 80 (weight) percent water. . Alcohols such as ethyl alcohol and isopropyl alcohol may be used at low concentrations (about 0.5% by weight of the formulation) to promote hair penetration and / or reduce odor.

vii. Viscosity modifier The formulation may comprise one or more viscosity modifiers such as thickeners. Such drug classes include viscous liquids such as polyethylene glycol; semi-synthetic polymers such as semi-synthetic cellulose derivatives; synthetic polymers such as carbomers, poloxamers and polyethyleneimines (eg PEI-10); acacia, tragacanth, alginate ( Naturally occurring polymers such as sodium alginate, carrageenan; vegetable gums such as xanthan gum; petrolatum; waxes; particulate associated colloids such as bentonite, colloidal silicon dioxide and microcrystalline cellulose; PPG-2 hydroxyethyl coco / Surfactants such as isostearamide; emulsifiers such as distealess-75 IPDI; salts such as sodium chloride; and combinations thereof include, but are not limited to.

viii. Antioxidants One or more antioxidants may be included in the formulation. Examples include tocopherol, BHT, ascorbic acid, camelia sinensis leaf extract, ascorbyl palmitate, magnesium ascorbyl phosphate, carotenoid, resveratrol, triethyl citrate, arbutin, kojic acid, tetrahexyldecyl ascorbate, superoxide dismutase , Zinc, sodium metabisulfite, lycopene, ubiquinone, and combinations thereof, but are not limited to these.

ix. Opacifier The formulation may include one or more opacifiers. An opacifier is added to the formulation to make it opaque. Suitable opacifiers include, but are not limited to, glycol distearate and ethoxylated fatty alcohols.

c. Formulation form i. Spray The formulation may be in the form of a spray. Sprays usually include an active agent and a cosmetically acceptable carrier. In some embodiments, the carrier is water or a mixture of water and alcohol. Spray formulations are optionally antioxidants, sunscreens, vitamins, proteins, peptides, plant extracts, wetting agents, oils, softeners, lubricants, thickeners, hair conditioners, polymers and / or surfactants. including. The spray formulation preferably contains a preservative. In some embodiments, the formulation includes a fragrance. In some embodiments, the formulation includes a surfactant. In some embodiments, the formulation includes water, fragrance, preservative, and active agent. In some embodiments, the formulation includes water, preservatives, fragrances, activators and antistatic agents. In some embodiments, the formulation includes water, preservatives, fragrances, active agents, and hair conditioning agents. In some embodiments, the formulation includes water, preservatives, fragrances, activators and surfactants.

  The hair spray formulation may be dispensed from a container equipped with an aerosol dispenser or a pump spray dispenser. Such dispensers are known in the art and are commercially available from various manufacturers.

Spraying When dispensing a hair spray formulation from a pressurized aerosol container, a spray may be used to force the formulation out of the container. Suitable propellants include, but are not limited to, liquefiable gases or halogenated propellants. Examples of suitable propellants include dimethyl ether and hydrocarbon propellants such as propane, n-butane, iso-butane, CFCs, and CFC alternative propellants. The spray may be used alone or in combination.

  The amount of propellant may range from about 10% to about 60% by weight relative to the formulation. The propellant may be separated from the hair repair formulation, such as in a container with two compartments. Another suitable aerosol dispenser is a dispenser characterized by a propellant that is compressed air that can be filled into the dispenser using a pump or equivalent device prior to use. Conventional non-aerosol pump spray dispensers, or nebulizers, may also be used to apply the formulation to the hair.

ii. Conditioner The formulation may be in the form of a conditioner. Conditioners typically include an active agent in a suitable carrier. Conditioners also include cationic polymers derived from polysaccharides such as cationic cellulose derivatives, cationic starch derivatives, cationic guar derivatives and cationic locust bean gum derivatives, synthetic cationic polymers, mixtures or combinations of these agents. Is mentioned. The formulation may include other synthetic or natural polymers, or polymers derived from biological preparation processes, which are functional, eg suitable for cationic or neutral groups. These polymers may have a stabilizing or reinforcing action on the formulation and / or a conditioning action (deposition on the skin or hair surface).

  The active agent may be included at any suitable concentration. Typical concentrations of the active agent in the conditioner range from a small amount, such as about 0.01 (wt)%, preferably at least 0.1 (wt)%, to a large amount, such as up to 50 (wt)%. Preferably, the conditioner comprises an active agent at a concentration in the range of 0.1 wt% to 5 wt%, more preferably 0.1 wt% to 3 wt%. Although it is possible to include higher concentrations of active agent in the conditioner, such concentrations are usually not necessary to achieve the desired result.

iii. Shampoo The hair repair formulation may be in the form of a shampoo. Shampoos usually contain the active agent in a suitable carrier. The active agent may be included at any suitable concentration. Typical concentrations of active agents in shampoos range from small amounts, such as about 0.01 (wt)%, preferably at least 0.1 (wt)%, to large amounts, such as up to 50 (wt)%. Preferably the shampoo comprises an active agent at a concentration in the range of 0.1 (wt)% to 5 (wt)%, more preferably 0.1 (wt)% to 3 (wt)%. Although it is possible to include higher concentrations of active agent in the shampoo, such concentrations are usually not necessary to achieve the desired result.

  The shampoo may also include from about 0.5% to about 20% by weight surfactant material. Surfactants for use in shampoo compositions are well known in the art and are disclosed, for example, in Gallagher et al. US Pat. No. 6,706,258 and Geary et al. US Pat. No. 7,598,213. Yes.

iv. Creams, lotions, gels and brighteners Hair, skin or nail restoration formulations may be in the form of creams, lotions, gels or brighteners. Creams, lotions, gels or brighteners usually contain the active agent in a suitable carrier. The active agent may be included at any suitable concentration. Typical concentrations of active agents in creams, lotions, gels or brighteners are as small as about 0.01 (wt)%, preferably at least 0.1 (wt)%, up to 50 (wt)% etc. There is a range up to a large amount. Preferably the cream or lotion comprises the active agent at a concentration ranging from 0.1% (by weight) to 5% (by weight), more preferably from 0.1% (by weight) to 3% (by weight). Although it is possible to include higher concentrations of active agent in a cream or lotion, such concentrations are usually not necessary to achieve the desired result.

  The preparation may also contain oils, hair conditioners and / or thickeners depending on the use. Creams, lotions, gels or brighteners may contain fragrances, plant extracts and / or surfactants. Creams, lotions, gels or brighteners may be enclosed in tubes, tubs, bottles or other suitable containers.

v. Liquid Activator Formulations In some embodiments, a liquid active agent formulation is provided, which is mixed in combination with a second formulation, such as a colored or highlighting formulation. In these embodiments, the liquid active agent formulation may include any suitable concentration of the active agent in a suitable carrier, usually a diluent as described above. The concentration of active agent is suitable to provide a mixture with the appropriate final amount and final concentration of active agent.

  For example, the liquid active agent formulation can include a concentration of active agent from about 5% (by weight) to about 50% (by weight) or more. In a preferred embodiment, the liquid active agent formulation comprises about 20% (by weight) of active agent.

  In highlighting applications, prior to use, a sufficient amount of liquid active agent formulation is mixed with a sufficient amount of highlighting formulation to form a highlighting mixture containing the desired concentration of active agent. Typical concentrations of the active agent in the highlighting mixture range from a small amount, such as at least about 0.01 (wt)%, preferably at least 0.1 (wt)%, to a large amount, such as up to 50 (wt)% There is a width. Preferably the highlighting mixture comprises an active agent at a concentration ranging from 0.1% (by weight) to 5% (by weight), more preferably from 0.1% (by weight) to 3% (by weight). Although it is possible to include higher concentrations of active agent in the highlighting mixture, such concentrations are usually not necessary to achieve the desired results.

III. Usage A. Treatment of hair with colorants a. Application of the coloring formulation to the hair The coloring formulation is usually applied to the individual's hair according to the usual hair coloring procedures known to those skilled in the art. Usually, the hair coloring process involves two complementary processes: applying a bleach formulation to bleach the natural pigments of the hair and / or other artificial pigments present in the hair, and the dye precursor to the hair. It involves diffusing, followed by a coupling reaction to form a chromophore in the hair shaft, but this chromophore is too large to diffuse out of the hair. Bleach formulations usually contain bleaching agents that decolorize the hair and generate free thiol groups. The hair coloring formulation may be a highlighting formulation as formed by mixing the bleaching powder and the developer. More complex pigments may contain several precursors and multiple color formers and may participate in multiple reactions.

  The dye precursor may include several components each having a different function. The first component is usually an alkalinizing agent (usually ammonia such as monoethanolamine [MEA] and / or an ammonia substitute). Alkalizing agents play a number of roles in the hair colorant process, including expanding the hair fibers and assisting in the diffusion of the dye precursor. The dye precursor usually contains p-diamine and p-aminophenol. When the precursor penetrates the hair shaft, it is oxidized to an active intermediate. The intermediate then reacts with the color former to form a wash resistant dye. More specifically, the intermediate combines with another oxidation dye intermediate molecule in the presence of an oxidizing agent to form a large condensed ring pigment compound within the hair shaft. Since the fused ring product is too large to penetrate the hair shaft, the precursor intermediate needs to penetrate the hair shaft prior to the coupling reaction. The color former modifies the color produced by oxidation of the precursor compound. The main difference between a semi-sustained product and a sustained product is the alkalinizing agent and peroxide concentration. Cuticles do not swell significantly in the case of semi-persistent dyes, making dye penetration less efficient compared to persistently colored products.

  Some coloring formulations use a reducing agent such as sodium hydrogen sulfate to break disulfide bonds in the hair and allow the hair coloring dye to penetrate deeper into the hair. Specifically, the method includes reducing a part of a cystine disulfide bond in the hair shaft to a thiol group while breaking a hydrogen bond. This reduction process changes undesirable chemical and cosmetic properties of the hair.

  A shampoo and conditioning treatment may be performed after the hair dyeing process and the neutralizing rinse or acid balance adjusting shampoo contains cationic active softener and quaternary polymer in addition to cationic or amphoteric surfactant. . Alternatively, the active agent formulations described herein may be applied after the hair dyeing process and before the shampoo and / or conditioning treatment.

b. Application of the active agent formulation to the hair The active agent formulation may be applied simultaneously with the hair coloring formulation or after application of the hair coloring formulation. For example, the active agent formulation may be mixed with the hair coloring treatment, or a mixture containing both the active and hair coloring treatment may be applied to the hair.

  Alternatively, the active agent or formulation thereof is applied to the hair after it has been colored. The activator is usually applied on the same day as the coloring treatment, but may be applied later, such as within 1 to 2 weeks after the reducing agent treatment. Typically, the amount of active agent formulation (or mixture of active agent formulation and hair coloring formulation) applied is sufficient to saturate the hair. The active agent may be applied to the hair in a single application, or application of the active agent may be repeated one or more times. Usually, the amount of active agent formulation applied to each application is sufficient to saturate the hair. The volume of active agent formulation applied to the hair with each application may be from about 1 to about 100 mL per person depending on the length and volume of the hair. In some embodiments, application of the active agent is immediately after the first application (eg, within 10-15 seconds) or about 1, 5, 7.5, 10, 12.5, 15, 17.5 or It can be done again after 20 minutes.

  The active agent can be rinsed from the hair immediately after application, for example 10, 15, 25, 30, 45 or 60 seconds, or 2, 3, 4 or 5 minutes after application, or washed with shampoo. is there. Alternatively, the active agent is rinsed from the hair within about 30 minutes after application, preferably from about 5 to about 20 minutes, more preferably about 10 minutes after application of the active agent to the hair, depending on the type of hair. But you can.

  When the active agent formulation is used in combination with a hair coloring treatment and applied to the hair as a mixture, the mixture is left on the hair for the time required for the hair coloring treatment. Usually, the mixture is applied for about 10 minutes. About 10 minutes after application of the mixture, the mixture is removed from the hair according to standard methods of hair coloring treatment, such as rinsing and shampooing.

  The active agent formulation is rinsed from the hair after application. The hair may be rinsed and subsequently washed immediately after the final application of the active agent (eg, within 10-15 seconds of application). Preferably, the hair is rinsed after about 10 minutes or more after the final application of the active agent, such as about 15 to about 30 minutes, optionally about 20 minutes after reapplying the active agent to the hair. And / or wash.

  Active agents are usually washed from individual hair on the same day as application. In contrast, conventional permanents that use only hydrogen peroxide (and without the addition of an activator) typically do not wash at least 48 hours after application (hair before 48 hours have passed since conventional permanent treatment). Washing may significantly reduce the degree of curling of the hair and / or damage the hair).

  The formulations described herein improve hair quality such as appearance (eg, gloss) and feel, and reduce hair breakage when the hair is subjected to treatments such as coloring or wave perm.

  In some embodiments, the cut hair is 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50% or more after active agent treatment compared to untreated hair of the same individual. Decrease. Cut hair is a serious problem that occurs during coloring and other processing.

B. Chemical Treatment of Hair with a Reducing Agent In one embodiment, prior to treatment with an active agent, the hair is converted into a reducing agent for use in wave treatment (also referred to herein as hair perm or wave perm) and / or curl treatment of hair. I am serving.

a. Application of reducing agent to hair The first step in wave or curling hair is to cleave cysteine disulfide bonds to form free thiol moieties. The process of cleaving cysteine disulfide bonds is through the application of a reducing agent. The process of applying the reducing agent includes the following normal perm treatment and hair straightening procedures known to those skilled in the art. For permanent hair, for example, the hair is first washed and set on various sizes of permanent rods. Second, a reducing agent such as a thioglycolic acid reducing solution or lotion is applied to the hair. The hair is allowed to stand for the specified time, and then the thioglycolic acid solution is rinsed from the hair.

  Application of hydrogen peroxide during this process is optional. In some processes, such as when treating pre-chemically treated hair, hydrogen peroxide is usually not used. In other processes, such as when permanent treatment of virgin hair, hydrogen peroxide may be added. In these embodiments, hydrogen peroxide is usually added after rinsing the reducing agent. The hydrogen peroxide is then rinsed from the hair before the active agent is added.

b. Application of the active agent After the reduction treatment, one or more active agents or formulations thereof are applied to the hair. The drug is usually applied on the same day as the treatment with the reducing agent, but it may be applied later, such as within 1 to 2 weeks after the treatment with the reducing agent.

  Usually, the amount of active agent formulation applied is sufficient to saturate the hair. The drug is generally rinsed from the hair and washed with shampoo after the hair wave or curl is at the desired level. In some embodiments, the active agent is rinsed from the hair immediately after the final application of the active agent (eg, within 10, 15, 25, 30, 45, or 60 seconds of application). Alternatively, depending on the type of hair, the hair is rinsed and washed within about 30 minutes after application, preferably about 5 to about 20 minutes, more preferably about 10 minutes after the final application of the active agent to the hair. May be. The active agent can be rinsed from the hair within 10, 15, 25, 30, 45, 60 seconds of application to obtain the desired level of hair waving or curling.

  The active agent may be applied to the hair in a single application, or application of the active agent may be repeated one or more times. Usually, the amount of active agent formulation applied to each application is sufficient to saturate the hair. In some embodiments, the volume of active agent formulation applied to the hair in each application is about 1 to about 10 mL per perm rod. In some embodiments, application of the active agent is immediately after the first application (eg, within 10-15 seconds) or about 1, 5, 7.5, 10, 12.5, 15, 17.5 or It can be done again after 20 minutes. In some embodiments, the second application is about 7 minutes to about 10 minutes after the first application.

  The active agent is rinsed from the hair after application. The hair may be rinsed and washed immediately after the final application of the active agent (eg, within 10-15 seconds of application). Alternatively, the hair is rinsed after about 10 minutes or more after the final application of the active agent, for example, about 15 minutes to about 30 minutes, preferably about 20 minutes after reapplying the active agent to the hair, You may wash.

  Active agents are usually washed from individual hair on the same day as application. In contrast, conventional permanents that use only hydrogen peroxide (and without the addition of an activator) typically do not wash at least 48 hours after application (hair before 48 hours have passed since conventional permanent treatment). Washing may significantly reduce the degree of curling of the hair and / or damage the hair).

  The formulations described herein can be applied to the hair to improve hair quality such as appearance (eg, gloss) and feel, and to reduce hair breakage when subjected to subsequent treatments such as coloring.

  In some embodiments, the hair is 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50% after application of the active agent, or compared to untreated hair of the same individual, or Decrease more. Cut hair is a serious problem that occurs during coloring and other processing.

C. Treatment of skin or nails with an active agent In one embodiment, a formulation comprising one or more active agents is applied to the skin or nails. Application of the active agent formulation to the skin and nails can help repair disulfide bonds damaged by natural wear and natural aging.

  In some embodiments, the active agent formulation is in the form of a cream or lotion suitable for application to the skin or nails. In other embodiments, the active agent formulation is in the form of a gel or brightener suitable for application to the nail. Typically, the amount of active agent formulation applied is sufficient to treat keratin with damaged skin or nails. The active agent formulation may be applied to the skin or nails in a single application, or formulated to repair keratin damage and / or achieve the desired effect of strengthening the skin or nails. Application of the object may be repeated one or more times as necessary.

IV. Kits A kit for treating hair is provided. In one embodiment, the kit typically includes a first formulation for coloring hair. Hair coloring formulations usually include a reducing agent that can reduce disulfide bonds in the hair to produce free thiol groups. The kit also includes a second formulation containing an effective amount of the active agent.

  The kit may further comprise developer bottles, gloves, shampoos, conditioners and / or deodorants. Usually, instructions for using the kit are also provided.

  To ensure that the decolorizer (eg, peroxide) or colorant is stored separately from the active agent, the kit is typically provided with multiple containers (or multiple compartments within a given container).

a. First formulation The first formulation in the kit can be a color treatment. The first formulation may be formulated as two or more components that can be mixed together prior to application to the hair. For example, the first formulation may be in the form of a two component such as a dye precursor and an oxidizing agent. Usually, hair coloring formulations include a reducing agent capable of reducing disulfide bonds in the hair and generating reduced free thiol groups. Suitable reducing agents include thioglycolic acid, thiolactic acid, dihydrolipoate, thioglycerol, mercaptopropionic acid, sodium bisulfite, ammonium disulfide, zinc formaldehyde sulfoxylate, sodium formaldehyde sulfoxylate, sodium metabisulfite, Examples include, but are not limited to, potassium borohydride, PEGylated thiol and hydroquinone. The amount of reducing agent in the first formulation is sufficient to break a sufficient number of disulfide bonds to effectively diffuse the hair coloring component as understood by those skilled in the art.

  The components of the first formulation may vary depending on the target hair coloring treatment (such as slightly continuous, semi-persistent or continuous hair coloring), the texture of the hair, the sensitivity of the user's skin, and the like. Hair coloring formulations for different hair coloring treatments, hair texture and hair sensitivity are known to those skilled in the art.

b. The active agent formulation The second formulation comprises one or more active agents in an effective amount. Suitable formulations containing the active agent are described above. The second formulation may be in any form as long as it is in a suitable form. Suitable forms include, but are not limited to, low to moderately viscous liquids, lotions, emulsions, mousses, sprays, gels, creams, shampoos, conditioners and the like. The second formulation will be placed in a suitable container depending on the form of the formulation.

  In one embodiment, the active agent formulation is provided as two or more separate components. For example, the active agent may be provided as a dry powder in a sealed package and the excipient may be provided in a vial or other container. Mixing containers suitable for active agents and excipients may be provided.

  In some embodiments, the active agent formulation (or second formulation) is mixed with the first formulation (or hair coloring treatment) and the mixture is applied to the hair.

c. Other materials in the kit The kit optionally includes shampoos and conditioners. Suitable shampoos and conditioners include, but are not limited to, LiQWd® Hydrating Shampoo and LiQWd® Hydrating Conditioner.

  The kit may further contain a deodorant. The deodorant can be incorporated into the first or second formulation or a mixture thereof. Alternatively, before or after washing the second formulation from the hair, the deodorant is placed in a container suitable for use. Several suitable deodorants are known to those skilled in the art.

  It is to be understood that the disclosed methods and formulations can be varied and are not limited to the specific methodologies, protocols, and reagents described. Also, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the scope of the invention, which is limited only by the scope of the appended claims. Is also understood.

Example 1: Color retention and texture of colored hair treated with an active agent formulation Overview Three hair samples were obtained from a human subject and cut into ½ inch widths.
Coloring Formulation: Permanent hair coloring formulation was obtained from L'Oreal® permanent hair coloring service (L'Oreal® Majoryl permanent color # 10, 20 volume peroxide).
Activator formulation: 200 mg concentration of maleic acid in 10 g total solution (water) was used.

Method The hair sample was washed with a clean shampoo and then dried with a towel. The sample was then colored with L'Oreal® permanent hair color service, which was left on the hair sample for about 35-40 minutes.

  The first pigmented hair sample (“control”) was then rinsed, washed 5 times with Liqwd® Hydrating Shampoo and Conditioner and then photographed.

  The active agent formulation was applied to the second and third colored hair samples via a spray bottle and massaged with fingers. The active agent formulation was left on the second hair sample for about 1 minute and left on the third sample for about 10 minutes. The hair samples were then rinsed and washed 5 times with Liqwd® Hydrating Shampoo and Conditioner before testing.

result:
Hair samples treated with the active agent formulation showed improved color retention, increased brightness and reduced curl compared to the control. Hair samples treated with the active agent formulation were smooth to the touch, with reduced curl, added gloss, and an overall healthier appearance compared to the control.

Example 2: Comparison of color retention between conventional perm-treated hair and perm-treated hair using an active agent formulation Method A 1/2 inch wide hair sample obtained from a human subject is cleaned shampoo And then dried with a towel. Ammonium thioglycolate or dithiothreitol was mechanically pulled through the hair several times with a coarse and fine comb and then left on the hair for 10 minutes to 1 hour. The hair was then rinsed with water for 30 seconds to 1 minute and dried with a towel.

  The active agent formulation (maleic acid in water) described in Example 1 was then applied with a needle nose applicator, soaking the hair and letting it stand for 7.5 minutes. This process was repeated for a total of 15 minutes. The hair was then rinsed for 1-2 minutes, washed with shampoo, and then conditioned with various salon shampoo and conditioner brands such as LiQWd® Hydrating Shampoo and Hydrating Conditioner.

  A second sample of hair was straightened as described above, but hydrogen peroxide was used instead of the active agent formulation. The hair sample was washed and conditioned repeatedly.

Hair color comparison:
Both hair samples were washed 5 times using LiQWd® Hydrating Shampoo and Liqwd® Hydrating Conditioner, and then the samples were tested for color retention.

Results The hair sample treated with the active agent formulation exhibited a color intensity close to that of the hair sample before the first wash compared to the hair treated with hydrogen peroxide.

Example 3: Comparison of hair treated with an active agent formulation at the same time as a highlight treatment formulation and hair treated with a highlight treatment formulation alone The active agent formulation of Example 1 is 10 g total solution (water). It contained 2.0 g maleic acid at a concentration of 2.0 g.

  Two samples of human hair were tested. Samples were obtained from the same head with a width of 1 inch and divided in half. The color was medium brown, which was previously colored with an unknown professional hair colorant.

  Sample 1 having a width of 1/2 inch and an length of 8 inches was decolorized with a conventional highlighting component mixed with the active agent formulation. One ounce Jico Verocolor Veroxide developer-20 volumes and 1 ounce Jico Verolight powder bleach were mixed to form a highlighting formulation. 9 mL of the activator formulation was then added to the highlighting formulation to form a mixture.

  The mixture was applied to the hair of Sample 1 with an application brush placed in an aluminum foil. The sample was then wrapped in foil and processed for 35 minutes. The sample was rinsed and washed once with shampoo.

  A control sample 2, 1/2 inch wide and 8 inches long, was decolorized with a conventional highlighting component without the use of an active agent formulation. One ounce Jico Verocolor Veroxide developer-20 volumes and 1 ounce Jico Verolight powder bleach were mixed to form a highlight treatment formulation with a creamy consistency.

  The highlight treatment formulation was applied to the hair of Sample 2 with an application brush in an aluminum foil shape. The sample was then wrapped in foil and processed for 35 minutes. The sample was rinsed and washed once with shampoo.

Results A significant difference in hair quality was observed between Sample 1 and Sample 2. Sample 1 hair was softer, non-curly, hydrated, and glossier than Control Sample 2.

  Both swatches are washed and conditioned 5 times or more, and swatch 1 (treated with a mixture of highlighter formulation and activator formulation) is similar to control swatch 2 (treated with highlighter formulation only) A significant advantage was seen.

Example 4: Comparison of hair treated with a bleach treatment formulation and simultaneously coated with an active agent formulation and hair treated with only a bleach treatment formulation Summary Two hair samples were obtained from a human subject and the width Cut to 1/2 inch.

Method (1) A 0.5 oz powder bleach (Clair Professional, Basic White) and a 0.5 oz conditioning cream developer (Redken, Blonde Icing) were used together to form a bleaching mixture. 3.5 g of 2- (methacryloyloxy) ethane-1-aminium (Z) -3-carboxyacrylate (12 wt% in water) was added to the bleaching mixture and mixed thoroughly with a brush.

  (2) The prepared bleaching mixture was brushed onto the hair sample to completely coat the hair bundle. Hair coated with the mixture was wrapped in aluminum paper and allowed to stand under ambient conditions for 2 hours.

  (3) After bleaching for 2 hours, the hair sample was washed with shampoo, and then the hair was air-dried.

Results A significant difference in hair quality was observed between Sample 1 and Sample 2. The sample 1 hair has no discernable cuts, feels good and shows a healthy appearance, while the control (treated with the bleach treatment formulation only) has cut hair and feels good. It was rough, frayed and had an unhealthy appearance.

Example 5: Comparison of hair treated with a bleach treatment formulation and simultaneously coated with an active agent formulation and hair treated with a bleach treatment formulation only Summary Two hair samples were obtained from a human subject and the width Cut to 1/2 inch.

Method (1) A 0.5 oz powder bleach (Clair Professional, Basic White) and a 0.5 oz conditioning cream developer (Redken, Blonde Icing) were used together to form a bleaching mixture. 3.5 g of prop-2-ene-1-aminium (Z) -3-carboxyacrylate (10% by weight in water) was added to the bleached mixture and mixed thoroughly with a brush.

  (2) The prepared bleaching mixture was brushed onto the hair sample to completely coat the hair bundle. Hair coated with the mixture was wrapped in aluminum paper and allowed to stand under ambient conditions for 2 hours.

  (3) After bleaching for 2 hours, the hair sample was washed with shampoo, and then the hair was air-dried.

Results A significant difference in hair quality was observed between Sample 1 and Sample 2. The sample 1 hair has no discernable cuts, feels good and shows a healthy appearance, while the control (treated with the bleach treatment formulation only) has cut hair and feels good. It was rough, frayed and had an unhealthy appearance.

Example 6: Comparison of a conventional perm with a perm using maleic acid Overview A hair sample was obtained from a human subject and cut to a width of 1/2 inch.
Reducing agent: Ammonium thioglycolate (ATG) was obtained from a wave permanent kit manufactured by Zotos. Further, 10 g of a solution containing 300 mg of dithiothreitol was used as a reducing agent.
Activator formulation: Maleic acid at a concentration of 200 mg in 10 g of total solution (water) was used.

Method Method of Perming Hair Using an Active Agent The hair was washed with a clean shampoo, dried with a towel and then wrapped around a perm rod. Thereafter, ammonium thioglycolate or dithiothreitol was applied to the hair and left on the hair for 10 minutes to 1 hour. Thereafter, the hair was rinsed for 30 seconds to 1 minute, and then blotted with a towel and dried.

  The active agent formulation was applied to the hair with a needle nose applicator to immerse the hair. The active agent formulation was left on the hair for about 7.5 minutes. The hair was soaked twice in the active agent formulation and left twice for 7.5 minutes, for a total of 15 minutes. The hair was then rinsed with water for about 1-2 minutes and then unwound from the permrod. After the hair was unwound from the perm rod, the hair was washed with a shampoo and conditioned with various salon shampoo and conditioner brands such as LiQWd® Hydrating Shampoo and Hydrating Conditioner. The washing and drying process was repeated 40 times.

  The second part of the hair was permed as described above except that hydrogen peroxide was used instead of the active agent formulation.

Results Both permanents (using activator formulation or hydrogen peroxide) had only a slight reduction in overall curl after 40 washes and dryings with the same shampoo and conditioner. However, the appearance and feel of the permanent using the activator formulation was glossy and less curled compared to the permanent using hydrogen peroxide.

Example 7: Comparison of cut hair resulting from repeated application of conventional permanent and active agent formulations.
Method Two hair samples were obtained. Both samples were treated with dithiothreitol or ammonium thioglycolate as described in Example 4. One of the hair samples was then treated with the active agent formulation (maleic acid in water) and the other was neutralized with hydrogen peroxide. For hair treated with the active agent formulation, the process was completed on the same day. With hydrogen peroxide (conventional permanent agent), the process was completed after 3 days.

  This procedure was repeated 3 times over 48 hours for each hair sample.

Results Upon visual inspection, the second hair sample treated with the active agent formulation had little or no evidence of cut hair. However, the first hair sample treated with hydrogen peroxide had significant hair breakage.

Example 8: Comparison of the degree of damage to hair that has been straightened with a hair straightener made in Japan. Method Two hair samples, hair straightener treated in advance with a Japanese hair straightener (Yuko) First sample and no lye hair straightener (African Pride Miracle)
A second sample that had been subjected to straightening treatment in advance by Deep Conditioning was obtained. Samples were processed as described in Examples 4 and 5 using an activator formulation (maleic acid in water).

  Another hair sample was obtained that had been straightened with a no lye hair straightener (African Pride Miracle Deep Conditioning) in advance. The sample was treated with a conventional hair straight perm (Zotos).

Results No significant damage was seen on the hair samples treated with the active agent formulation. However, the sample treated with the conventional permanent agent showed considerable cut hair even during application.

Claims (1)

The invention described herein.